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International audience; Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.

Background: Chronic immunosuppression after solid-organ transplantation is associated with increased risk of developing malignancies. The purpose of this study was to determine the clinical characteristics and the outcome of thoracic malignancies in patients who have undergone solid-organ transplantation. Methods: Among a cohort of 2831 patients who received a transplant at our institution and were followed between 1984 and 2009, 24 patients (0.85%) developed thoracic malignancies. Risk factors for lung cancer, as well as demographic, cancer, and transplantation characteristics, were analyzed. Survival data were also collected. Results: Twenty-four patients were included (21 men, median age 61.7 years). Twenty-two patients were smokers. The most frequent histologic types were squamous cell carcinoma ( n = 11, 46%) and adenocarcinoma ( n = 9, 37%). The median time period between transplantation and diagnosis of lung cancer was 6.6 years. Ten lung malignancies occurred after kidney transplantation (0.5%), eight after liver transplantation (1.3%), and six after heart transplantation (2.8%). Seven patients underwent surgery, three had radiotherapy, four had chemotherapy, and six had multimodal treatment. The median survival time was 1.5 years, ranging from 6 months for stage IV to 3.7 years for stage I. Conclusion: Solid-organ transplantation is associated with a high risk of lung cancer and may have an important synergetic part with other risk factors for lung cancer (tobacco). However, survival rates from lung cancer in our study population are similar to those of nontransplanted patients. In addition, surgery can result in favorable survival results.

Benfluorex, an amphetamine derivative, was marketed as an adjunctive drug for patients with hypertriglyceridemia or diabetes with overweight. We describe here 5 cases of pulmonary arterial hypertension (PAH) associated to a treatment with this drug and notified to the Midi-Pyrenees Pharmacovigilance Centre. All cases are women, exposed to benfluorex during at least 3 years. In most of cases, benfluorex was used off-licence, for overweight.

Platypnea orthodeoxia syndrome (POS) is a rare situation with hypoxia and breathlessness varying between upright and recumbent position. A mechanical inter-atrial septum distortion, causing redirection of flow from the right to the left atrium through a patent foramen ovale (PFO), despite normal pulmonary pressure, is suggested to explain POS. Prevalence of predisposing anatomical factors remain little known. Methods All patients who underwent a PFO closure for a POS were retrospectively included from 2 CHU. Aetiologies were investigated. Results 67 patients (Median age 72 y.o., interquartile 61-80; 58.2% men) were included. All patients had dyspnea (76.2% NYHA III or IV, 53.7% under oxygen-therapy). The remaining patients had a refractory hypoxemia (38.2%) without POS. The most frequent predisposing anatomical factor was an enlarged or unwound aorta (n=29, 43.3% 95CI 31.2-56.0) with an aortic aneurysm in 25 patients (37.3%, 95CI 25.8-50.0). Other factors identified were pneumonectomy (n=8, 11.9% CI95 5.3-22.2), a history of cardiac surgery (n=7, 10.5%, 95CI 4.3-20.3), mechanical ventilation (n=6, 9.0% 95CI 3.4-18.5), kyphoscoliosis (n=4, 6.0% 95CI 1.7-14.6), hepatomegaly (n=4, 6.0% 95CI 1.7-14.6, 2 patients with hepato-renal polycystic disease, one hemochromatosis and one cirrhosis), right ventricle failure (n=2,3.0% 95CI 0.4-10.4), pericardial effusions (n=2,3.0% 95CI 0.4-10.4), right ventricle arrhythmogenic dysplasia (n=2,3.0% 95CI 0.4-10.4), diaphragmatic paralysis (n=1, 1.5% 95CI 0.1-8.0), carcinoid syndrome with tricuspid regurgitation (n=1, 1.5% 95CI 0.1-8.0), a right atrium pace-maker lead (n=1, 1.5% 95CI 0.1-8.0) and a takotsubo syndrome (n=1, 1.5% 95CI 0.1-8.0). Conclusion Aortic aneurysm and pneumonectomy are the most frequent and well known situation leading to a POS. Other causes less known were observed such as hepato-renal polycystic kidney, or atrial pacemaker probe that may be underdiagnosed in clinical practice.

Platypnea orthodeoxia syndrome (POS) is a rare condition with right to left shunting through a Patent Foramen Ovale (PFO) that results in oxygen desaturation during postural changes. Few series are available on the functional status after PFO closure. The aim of our study was to describe the impact of PFO closure in this population. Methods We retrospectively included 24 consecutive patients with dyspnea related to POS, aged 73.6±9.6 years old (min 52, max 86, 62.5% male) who were referred for PFO closure between Oct. 2006 and july 2011 in the Toulouse Rangueil universitary hospital. Follow-up data were available in May 2012. Results At baseline, all patients had dyspnea (58.3% NYHA 4). Eight patients (33.3%) had a history of stroke attack. POS was related to right pneumonectomy in 3 patients (12.5%), ascending aortic ectasy in 11 patients (45.8%), hepato-renal polycystic disease in 2 patients (8.3%). Aneurysm of the inter-atrial septum was observed in 12 patients (50%). PaO2 was lower in erect position compared to recumbent position (50.4±6.8 versus 72.6±12.5 mmHg, p=0.0005). Closure of the PFO was performed percutaneously in 24 patients (100%). An additional surgical PFO closure was necessary in 1 patient because of significant residual shunting. PaO2 in erect position was significantly increased after closure (p=0.0254). During follow-up, 4 patients (16.7%, p=0.125) had a complete relief of their symptoms after closure. Dyspnea was significantly improved according to NYHA functional class (p=0.023). General status improved in 75% patients (p=0.025). Eight patients died (33.3%). Four deaths (50%) were related to stroke attacks at respectively 18 days, 3,11 and 39 months after PFO closure. Four deaths were not related to cardiac issue. Conclusion Patients referred for PFO closure for POS are old and at high risk of mortality, particularly from stroke attacks. PFO closure is associated with an improvement of the functional NYHA class and of the general status.

Auteur groupe collaboratif RaDiCo team; International audience; Introduction: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.Methods: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution).Results: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified.Conclusions: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF.Trial registration: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).